Chiral stationary phases polysaccharide derivatives

According to their chemical structures, CSPs can be divided into three different groups. A multitude of chiral stationary phases is derived from (modified) natural or synthetic polymers, e.g., the polysaccharides, proteins or polyacrylamides. A second type of selectors is based on large chiral ring systems, such as cyclo-dextrins, macTocycKc antibiotics, and crown ethers. The last group comprises moleailes of small and medium size, such as amino acids and their derivatives, alkaloids, and fuUy synthetic selectors. 

Temperature is also an important parameter for controlling the resolution of enantiomers in HPLC. The enthalpy and entropy control of chiral resolution on antibiotic CSPs is similar to the case of polysaccharide-based CSPs (Chapter 2). Armstrong et al. [1] have studied the effect of temperature on the resolution behavior of proglumide, 5-methyl-5-phenylhydantoin and A-carbamyl-D-pheny-lalanine on the vancomycin column. The experiments were carried out from 0°C to 45°C. These results are given in Table 6 for three chiral compounds. It has been observed that the values of k, a, and Rs for the three studied molecules have decreased with the increase in temperature, indicating the enhancement of chiral resolution at low temperature. In another work, the same workers [22] have also studied the effect of temperature on the resolution of certain amino acid derivatives on the teicoplanin chiral stationary phase. They further observed poor resolution at ambient temperature, whereas the resolution increased at low... 

Kaida, Y. and Okamoto, Y. (1992) Optical resolution by supercritical fluid chromatography using polysaccharide derivatives as chiral stationary phases, Bull. Chem. Soc. Jpn. 65, 2286-2288. 

Franco, P., Senso, A., Oliveros, L., and Minguillon, C. (2001) Covalently bonded polysaccharide derivatives as chiral stationary phases in high-performance liquid chromatography, J. Chromatogr. A 906, 155-170. 

HPLC was used to evaluate the enantiomeric resolution of dihydrope-pidine enantiomers (including nimodipine), using phenylcarbamates of polysaccharides as a chiral stationary phase [35]. A column (25 cm x 4.6 mm) packed with the arylcarbamate derivatives of amylase, cellulose, and xylem was used. Detection was effected using polarimetry at 435 nm. Using xylem bis-(3,5-dichlorophenylcarbamate) and a mobile phase (flow rate of 0.5 mL/min) of 0.1%, diethylamine in hexane-propan-2-ol (17 3) yielded separation of nimodipine. 

Y. Okamota and Y. Kaida, Polysaccharide derivatives as chiral stationary phases in HPLC, / High Resolution Chromatogr. 13 (1990), 708-712. 

Fig. 7.5 Su mma7 of the chemical structures and tradenames of the most important cellulose and amylose derivatives incorporated in polysaccharide-type chiral stationary phases.

Krause, K. Girod, M. Chankvetadze, B. Blaschke, G. Enantioseparations in normal- and reversed-phase nano-high-performance liquid chromatography and capillary electrochromatography using polyacrylamide and polysaccharide derivatives as chiral stationary phases. J. Chromatography A 1999, 837 (1-2), 51-63. 

Chen XM, Yamamoto C, Okamoto Y (2007) Polysaccharide derivatives as useful chiral stationary phases in high-performance liquid chromatography. Pure Appl Chem 79 1561-1573... 

Chiral stationary phases can exist in different forms [10] (see Fig. 8). Some selectors can be used as particulate phase materials, such as polymeric cellulose triacetate. Polymeric cellulose and amylose derivatives are often coated onto silica carrier particles so that only 20% of the CSP consists of the chiral selector. This combination of stationary phase and chiral polymer combines good chromatographic properties (due to the homogeneous particle size distribution) with a high density of chiral adsorption sites in the polysaccharide derivatives. Another approach is selected for the so-called brush-type CSPs. In these, the chiral selector is covalently bound to the surface of the silica particles. These phases show high chemical inertness and allow the use of a multitude of different mobile phases. 

Chiral polymers can be obtained in two different ways. The use of a chiral catalyst during polymerization can lead to helical structures, as observed in polysaccharides. The other synthesis path uses chiral monomers, which are polymerized to give a chiral polymer capable of folding to a supramolecular stmcture [20]. For application in HPLC, all of these polymers must be coated onto silica, since they are imable to withstand the high pressures encountered in HPLC. Currently, chiral stationary phases based on polyacrylates or polymethacrylates play only a minor role. Chirasphere (Merck) is derived from a silica material coated with poly(N-acryloyl-(S)-phenylalanine ethyl ester) and can be used for the separation of P-blockers in the normal-phase mode. The chiral polymethacrylates Chiralpak OP and Chiralpak OT (Daicel) are able to separate aromatic compounds into their enantiomers. 

Chiral separation of flavonoids has also been carried out by chromatographic systems by using a chemically bonded chiral stationary phase or by the addition of chiral mobile phase additives (reviewed by Yanez et al. ). These chiral polymer phases can be further subdivided into polysaccharide-derived columns, and cyclodextrin and mixed cyclodextrin columns. With regard to chiral mobile phase additives, the addition of an optically active molecule to the mobile phase can facilitate separation of enantiomers on conventional stationary phases. Cyclodextrin as a chiral additive is widely used to separate enantiomers mainly by capillary electrophoresis (CE), as discussed in Section 3.6.2.I. Table 3.7 summarizes the most habitual HPLC procedures employed for the analysis of various classes of food flavonoids. 

Zhang T, Nguyen D, Franco P. Reversed-phase screening strategies for liquid chromatography on polysaccharide-derived chiral stationary phases. J. Chromatogr. A 2010 1217 1048-1055. 

These polysaccharide-based stationary phases appear to be the most useful in organic, bio-organic and pharmaceutical analysis. Of the above-mentioned derivatives three of them, namely cellulose tris-(3,5-dimethylphenylcarbamate), amylose tris-(3,5-dimethylphenylcarbamate) and cellulose tris-(4-methylbenzoate), have very complementary properties and numerous publications have demonstrated that they have been able to achieve the chiral resolution of more than 80% of the drugs currently available on the market. " These CSPs are known under the commercial names, Chiralcel OD-H , Chiralpak AD and Chiralcel OJ , respectively (Figure 4). Their very broad enantiorecognition range is also the... 

Figure 35 CEC enantioseparations of 2-(benzylsulfinyl)benzamide in capillaries packed with derivitized with differing amounts of the polysaccharide derivative cellulose tris(3,5-dichlorophenylcarbamate). The stationary phase contained (a) 4.8%, (b) 1.0%, and (c) 0.5% (w/w) of the chiral selector. (Reprinted from Ref. 1 56, with permission.)...

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